Tight glucose control lowers cardiovascular complication risk by about 50 percent in those with type 1 diabetes

For the first time, research has shown that "lowering glucose, or blood sugar, levels cuts the risk of getting cardiovascular complications by about 50 percent in people with type 1 diabetes," according to Saul Genuth, M.D., professor of medicine at the Case Western Reserve University (Case) School of Medicine and an endocrinology specialist at University Hospitals of Cleveland.

Genuth chairs the follow-up study of Diabetes Control and Complications Trial participants, called the Epidemiology of Diabetes Interventions and Complications study, which has been examining the long-term effects of prior intensive versus conventional blood glucose control and is responsible for the finding, which was presented this week at the American Diabetes Association (ADA) annual meeting in San Diego.

Researchers announced the finding, that a significantly lower risk of heart disease can now be added to the list of proven long-term benefits of tight glucose control in people with type 1 diabetes, after analyzing cardiovascular events such as heart attack, stroke and angina in patients who took part in the DCCT years ago.

"The longer we follow patients, the more were impressed by the lasting benefits of tight glucose control," said Genuth, an alumnus of the Case School of Medicine. "The earlier intensive therapy begins and the longer it is maintained, the better the chances of reducing the debilitating complications of diabetes."

The DCCT was a multicenter study that compared intensive management of blood glucose with conventional control in 1,441 people with type 1 diabetes. Patients aged 13 to 39 years were enrolled in the trial between 1983 and 1989. Those randomly assigned to intensive treatment kept glucose levels as close to normal as possible with at least three insulin injections a day or an insulin pump, guided by frequent self-monitoring of blood glucose. Intensive treatment meant keeping hemoglobin A1c (HbA1c) levels as close as possible to the normal value of 6 percent or less. (The HbA1c blood test reflects a person's average blood sugar over the past two to three months.) Conventional treatment at the time consisted of one or two insulin injections a day with daily urine or blood glucose testing.

In 1993, researchers announced the DCCTs main findings: intensive glucose control greatly reduces the eye, nerve and kidney damage of type 1 diabetes. Tight control also lowers the risk of atherosclerosis, according to a study of DCCT participants published in 2003. But what's most remarkable about intensive control, the researchers say, is its long-lasting value.

After six years of the DCCT, HbA1c levels averaged seven percent in the intensively treated group and nine percent in the conventionally treated group. When the study ended, the conventionally treated group was encouraged to adopt intensive control and was shown how to do so, and researchers began the long-term follow-up of participants. To the researchers' surprise, the benefits of the original six years of intensive control have persisted despite the fact that both groups' HbA1c values have leveled off at about eight percent after a rise in blood glucose in the intensively treated group and a drop in blood glucose in those formerly on conventional treatment.

In results announced at the ADA meeting, among the 1,375 volunteers continuing to participate in the study, the intensively treated patients had less than half the number of cardiovascular events than the conventionally treated group (46 compared with 98 events). Such events included heart attacks, stroke, angina and coronary artery disease requiring angioplasty or coronary bypass surgery. Thirty-one intensively treated patients (four percent) and 52 conventionally treated patients (seven percent) had at least one cardiovascular event during the 17 years of follow-up. The average age of participants is 45 years; 53 percent are male.

"The risk of heart disease is about 10 times higher in people with type 1 diabetes than in people without diabetes. It's now clear that high blood glucose levels contribute to the development of heart disease," said David Nathan, M.D., of Massachusetts General Hospital, who co-chaired the DCCT/EDIC research group and presented the results. "The good news is that intensively controlling glucose significantly reduces heart disease as well as damage to the eyes, nerves and kidneys in people with type 1 diabetes. Tight control is difficult to achieve and maintain, but its advantages are huge."

"The take-home message is that good glucose control should be started as early as possible to delay or prevent serious diabetes-related complications," said Alan D. Cherrington, Ph.D., president of the American Diabetes Association.

Is glucose control just as important for people with type 2 diabetes? "There is a strong and growing body of evidence that everyone with diabetes gains from strict blood glucose control," said Catherine Cowie, Ph.D., who oversees EDIC for the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

DCCT and EDIC were funded by the NIDDK and other parts of the National Institutes of Health (NIH) under the Department of Health and Human Services. Genentech, Inc., also supported the studies through a cooperative research and development agreement with the NIDDK. The NIH also funds a great deal of research aimed at developing new approaches to help patients control diabetes, which is difficult for many people.

About 18.2 million people in the United States have diabetes, the most common cause of blindness, kidney failure, and amputations in adults and a major cause of heart disease and stroke. At least 65 percent of people with diabetes will die from a heart attack or stroke, yet two out of every three people with diabetes are unaware of their increased risk.

Type 1 diabetes accounts for up to 10 percent of diagnosed cases of diabetes in the United States (up to 1 million people). This form of diabetes usually strikes children and young adults, who need several insulin injections a day or an insulin pump to survive. Insulin, though critical for controlling blood glucose, is no cure. Most people with type 1 diabetes eventually develop one or more complications, including damage to the heart and blood vessels, eyes, nerves or kidneys.

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